The thematic hypothesis of the proposal is that ARDS results from dysregulated inflammation due, in part, to endothelial cell dysfunctional and injury. The hypothesis will be addressed by a multidisciplinary research program featuring a combination of interrelated clinical and basic investigations designed to generate new knowledge that will improve our understanding of the pathobiochemistry of ARDS, its treatment, and prevention. By orienting the proposal around the endothelial cell, and the molecular events that influence cell-cell and cell-matrix interactions, all projects interacts and intrinsically reinforce each other in almost every phase of their studies. The "intellectual structure" of the SCOR is as follows: Projects 1:Novel Inflammatory Responses of Injured Endothelium and Project 2: Dysregulated Expression of Signaling Molecules in Acute Lung Injury investigate proinflammatory cell-cell interactions; Project 3: Molecular Analysis of Integrin Receptors of Platelet and Endothelial Cells addresses cell-cell and cell-matrix mechanisms relevant to a variety of regulated and dysregulated interactions at the alveolar capillary membrane; Project 4: Nitric Oxide-mediated Responses in Acute Lung Injury and Project 5: Regulation of Inflammatory Lipids in Acute Lung Injury explore mechanisms of inflammation control. The Clinical Core (Core B) furnish the real test for the entire SCOR proposal by providing the clinical model in which the hypotheses espoused will be tested. The proposal offers an established research program, proven multidisciplinary collaborative interactions and a rich environment for productive basic and clinical research.